The goal of this predoctoral training program is to provide students with the intellectual and technical skills required to solve important and complex biological problems that can be most effectively addressed by studies at the chemistry-biology interface, and to create a group of graduating chemists and biologists who can effectively communicate and function successfully in multidisciplinary teams. The focus of the training program is mechanistic chemistry of biomolecules, which is a theme that is of special interest to a significant population of faculty and students on campus, and provides an excellent model system for the application of chemical tools to solve important biological problems. The Program involves 29 participating faculty from The Wistar Institute and two separate Schools within the University of Pennsylvania, The School of Medicine and The School of Arts and Sciences. Participating students come primarily from two graduate groups that span institution and school boundaries, the Graduate Group in Chemistry and the Graduate Group in Biochemistry and Biophysics. Students typically join the program when they matriculate and a subset of these students is funded on the training grant after they have chosen a thesis laboratory at the beginning of their second year. We request funding for 9 students. To insure cross-fertilization between the chemistry and biology students, those in the OBI program carry out dissertation research at the chemistry-biology interface with a CBI trainer and also participate in the following activities: (1) A course curriculum that crosses the chemistry- biology academic boundary and centers around the mechanistic chemistry of biomolecules, (2) A student run speaker-invited thrice-yearly Chemical Biophysics mini-symposia seminar series centered around the chemistry-biology interface, (3) A monthly luncheon in which CBI students and faculty informally discuss their research among themselves, and (4) An annual Chemistry-Biology Interface Retreat in which students interact and present their work to each other and other trainees and trainers. The program also has effective mechanisms in place for instruction in the responsible conduct of research and the recruitment of underrepresented minorities, the disadvantaged and the disabled. A training committee is comprised of roughly equal faculty representation from the three participating programs and trainee representatives, which meets annually. The training committee is responsible for selecting students for training slot positions, insures equitable distribution of students, encourages application from underrepresented minorities, the disadvantaged and disabled and administers other functions of the grant.